Evidence for uncoupled respiration in thyrotoxic and epinephrine-stimulated myocardium

Abstract

Oligomycin, an inhibitor of phosphorylation-dependent respiration in mitochondria, was used to operationally define that portion of the oxygen consumption of the arrested perfused rat heart not coupled to phosphorylation. Evidence is presented to document the analogy of the effects of oligomycin in the intact tissue to those seen in mitochondria. Potassium arrest (31 m[image]) was used to eliminate inotropic and chronotropic contributions to Qo2. The Qo2 of thyrotoxic hearts was uninhibited by oligomycin while that of controls was decreased by 18%, suggesting an increase in uncoupled respiration in intact thyrotoxic myocardium. The "metabolic" or "oxygen wasting" stimulation of Qo2 by epinephrine was not inhibited by oligomycin and was not significant in thyrotoxic hearts. The presistence of this effect in the presence of oligomycin suggests that the epinephrine induced increase of electron flow to oxygen is not coupled to phosphorylation, and offers an alternative hypothesis to stimulation of ATP utilizing cycles as an explanation for the adrenergic calorigenic effect. The implications of this uncoupled respiration for the myopathies of thyrotoxicosis and pheochromocytoma are discussed.